High virus burden together with depletion of CD4+ T cells is correlated with the progression of human immunodeficiency virus (HIV)-1 infection towards acquired immunodeficiency syndrome (AIDS), which is sustained by high virus replication and ongoing infection of target cells. HIV treatment is presently achieved through highly active antiretroviral therapy (HAART), which aims to maximize life expectancy while maintaining quality of life and minimizing drug toxicity. However, lifelong treatment with HAART is needed to maintain suppression of the viral load below 50 copies/ml because a cure is not possible with currently available agents (Lucas et al., 2005, J. Antimicrob. Chemother., 55, 413-6). Further, growing drug resistance seen in HIV/AIDS patients subjected to therapy and newly acquired HIV-1 infections underscores the requirement for new antiretroviral agents, as well as increasing the robustness of existing therapies.
For rational drug design to inhibit retrovirus infections, different stages of the virus replication cycle have been targeted (Li et al., 2005, Curr. Opin. Investig. Drugs, 6, 148-54). These steps include virus penetration, un-coating and/or virus adsorption to its cellular receptor, transcription of the viral RNA genome to proviral DNA (reverse transcription), transactivation of viral mRNA transcription and translation, assembly process and virus release (Li et al., 2005, above), although reverse transcriptase (RT) inhibitors have been proven to be the most effective agents to date (Wainberg et al., 2005, Antivir. Ther., 10, 13-28). However, emergence of drug resistance in patients treated with reverse transcriptase inhibitors is a major limitation of antiviral therapy (Salama et al., 2006, Infect. Disord. Drug Targets, 6, 107-19).
Among natural products with anti-HIV-1 properties, several agents have been isolated from algae and cyanobacteria (Schaeffer et al., 2000, Ecotoxicol. Environ. Sal, 45, 208-27), snake venom (Soares et al., 2003, Toxicon, 42, 855-68) and humics (Schneider et al., 1996, Virology, 218, 389-95). Humics are a soil- and water-derived heterogeneous mixture of polydisperse polymers in the molecular weight range from a few hundred to tens of thousands that have been studied for their antiretroviral properties (Leenheer et al., 2003, Environ. Sci. Technol., 37, 18A-26A; Laurberg et al., 2003, Biofactors, 19, 145-53).
Humic polyphenols and quinonoids represent a fraction of humic substances presenting complex binding interactions, self-assembling interactions, reduction/oxidation interactions and free-radical quenching antioxidant behavior (Bruccoleri et al., 2000, University of Calgary, PhD Thesis, p. 92-113; Bruccoleri et al., 2001, Molecular modeling of humic substances, in Ghabbour, E. A. and Davies, Geoffrey, eds., Humic substances—Structures, models and functions: Cambridge, Royal Society of Chemistry, p. 193-208; Gamble et al., 2005, Chemical stoichiometry and molecular level mechanisms as support for future predictive engineering. Chapter 6 In, eds. I. V. Perminova, N. Herkorn, and P. Baveye. Use of humic substances to remediate polluted environments: From theory to practice. NATO Science Series, Kluwer Academic Publisher, Dordrecht).
Two sesquiterpene hydroquinones, peyssonol A and peyssonol B, of the Red Sea algae Peyssonelia sp., have been shown to be potent inhibitors of HIV-1 and HIV-2 RT by acting as non-competitive RT inhibitors and repressors of HIV-1 replication (Loya et al., 1995, Arch. Biochem. Biophys., 316, 789-96).
A stable synthetic polymer with low toxicity and mutagenicity, HS-1500, synthesised by oxidation of hydroquinone at high pH, was found to inhibit HIV-1 in vitro, putatively through a hydrophobic/ionic interaction of HS-1500 with the V3 loop of the HIV-1 gp120 envelope protein (Schneider et al., 1996, above). Hydroquinones show limited cytotoxicity and carcinogenicity although bone marrow micronuclei have been reported. Further, epidemiological studies with hydroquinones have demonstrated lower death rates and reduced cancer incidences among individuals employed in the production of hydroquinones.
Due to the high ability of the virus to present mutational resistance and the emergence of drug-resistant strains of virus, there is a crucial need for the discovery and development of alternative anti-HIV agents, in particular active in inhibiting RT activity.
With rising concern about the spread of superbugs, healthcare trusts are increasingly looking to find new antimicrobial agents. Textile materials and clothing are known to be susceptible to microbial attack, by providing large surface areas and absorbing moisture required for microbial growth. Therefore, antimicrobial agents which can dye or stain textile or other materials have attracted significant attention in recent years because of the increasing concern on cross-contamination of diseases in public places and hospitals (Sun, 2005, J. Chem. Educ., 82, 60-64). In order to reduce rates of disease transmission and infection in hospitals, there is an increased interest in finding new antimicrobial agents with dye properties which can be used and incorporated into textiles for healthcare workers and patients and/or paint pigments for surfaces used in the healthcare venue.